Method for preparing aminocarboxylic acids



Patented Apr. 6, 1954 METHOD FOR PREPARING AMINO- CARBOXYLIC ACIDSMichailas Genas, Pari ciety Organico, Pa France s, France, assignor toSoris, France, a society of No Drawing. Application April 11, 1950,Serial No. 155,369

Claims. priority, application France April 14, 194%? 3 Claims.

This invention relates to the preparation of aminocarboxylic acids.

It is known how to prepare aminoacids by reacting ammonia withhalogenated acids in the so-called Hofimanns method of preparing amines.Thus, u-aminoacids have been prepared from the corresponding halogenatedacids, with good yields. It is also known however that the yield inamino-acids. decreases as the amino group is furtherremoved from in themolecule. For example, Flaschentrager and Halle, (Z. fiir physiol. Chem.159, 286, 1926) obtained, lO-aminoundecylic acid byreacting an alcoholicammonia. solution with 10-bromoundecylic acid with a yield of only about4%. In the opinion of those authors, this low yield is due to distanceseparating the functional groups.

According to Lutz- (Zentralblatt 1, 907, 1910) the principal, reactionproducts in the reaction of ammonia on ,8, 'y, 5 etc-halogenated acidsare 1 corresponding oxyacids. The proportion of the latterincreases'with the-distance separating the halogen and the carboxyl group.

Similarly, in the well-known work den der org. Chem. 1941), it is statedthat while the most convenient method of preparing a-aminoacids consistsof reacting ammonia on the a-halogenated acids (100. cit., p. 734) othermethods of synthesis are Die Methogenerally adopted in the case of thoseaminoacids in which the amine group is further removed from the carboxylgroup (p. 751).

It has already previously been discovered (of. French Patent 928,265,published November 24, 1947), that ll-bromoundecanoic acid is readilyconverted to ll-aminoundecanoic acid under the action of ammonia.However, this fact was considered as exception.

The applicant has now found that, contrary to the generally acceptedopinion, the distance between the carboxyl group and the halogen is notthe decisive factor and that what really matters is that the halogenshould be bonded to a primary carbon atom, that is a carbon atom bondedto two hydrogen atoms wherein X is a halogen atom. Thosehalogenocarboxylic acids that contain the group XCH2 can also be termedw-halogenocarboxylic acids. When such halogenated acids are subjected tothe action of aqueous, alcoholic or hydroalcoholic ammonia solutions,they are converted easily and the carboxyl group by Houben (vol. 4, 4thed.,

with a high yield into the corresponding w-aminocarboxylic acids, evenwhere the halogen. is bonded to a carbon atom at a position fartherremoved than fi-position from the carboxyl group, or in. other words,even though. the halogen atom may be bonded to a carbon atom separatedfrom the carboxyl group by a chain including more than one carbon atom.

These results are unexpected, and were unpredictable in view of theinformation tobe found in existing literature.

The above-mentioned reaction occurs at relatively low temperatures. Itsrate increases with the temperature. On the other hand the yield inamino-acids decreases as the temperature rises. Thus, if good yields areto be obtained, the reaction temperature should not exceed. 80 C. andshould preferably be lower than about 60 C.

The following examples will illustrate the invention withoutconstituting a limitationthereon. All parts are in weight.

Example 1 The starting material is l0-bromodecanoic acid, which may beprepared by any suitable method, as by oxidation of undecylenyl bromideor by reaction of an acetic solution of hydrobromic acid with10-oxydecanoic.

770 parts of lo-bromodecanoic acid are added in molten state into 00parts of a 25% aqueous ammonia solution. The mixture is agitated. Asomewhat fluid mass is formed and is maintained at about 15 C. Theprogress of the reaction is followed by dosing the amount of ammoniumbromide formed.

The reaction comes to an end after about 6 At the end of this time, thereaction mass is drain-ed. The resulting cake is washed with water, thentaken up with 10 liters of boiling water. The mass is then acidified toa pH of about 5.4. Some amount of oily product and an insoluble residueseparate from the mass, said residue chiefly comprising amino-didecanoicacid NH[(CH2)9COOH]2. This is filtrated hot and the clear filtrate isadjusted to a pH of from 6 to 6.3 by addition of a small amount ofammonia thereto. On cooling the lO-amino-decanoic acid cristallizes off.It is separated by a centrifuging step, and dried in a heating oven at80 C. 400 parts of IO-amino-decanoic acid melting at 177 C. are thusobtained. Another 40 parts of the acid are recovered from themotherliquor. The yield is 77% of theoretical.

Example 2 A mixture of l-bromodecanoic acid, 200 parts ethyl alcohol and300 parts aqueous ammonia solution is allowed to stand 10 days at 10 C.The mixture is then heated to the boil, whereupon the excess ammonia iseliminated and part of the alcohol distils away. After practically allthe excess ammonia has been removed the mixture is acidified withhydrochloric acid to pH 3-4. A slightly cloudy solution is obtained ofthe hydrochloride of the aminoacid, which is clarified by hotfiltration. The filtrate is adjusted with ammonia to a pH higher than6.6. On cooling the IO-aminodecanoic precipitates. This acid iscentrifuged, washed with water and dried in an oven at C. 51 parts ofpractically pure lo-aminodecanoic acid are obtained.

Example 3 Q-bromononanic acid (M. P. 33 C.) was prepared by reactingbromine with the silver salt of the ethyl monoester of sebacic acid andsubsequent hydrolysing the resulting ethyl bromononanoate to obtain freebromo-acid (Ber. '75,

291, 1942). 118 parts of this acid are added to 1 parts of a 27% aqueousammonia solution. The mixture is subjected to agitation and maintainedin a temperature range of from 0 to 5 C.

for 20 days. The reaction mixture is then caused NHE (CH2) sCOOI-I] 2 isseparated. From this filtrate, on cooling, 52 parts S-aminononanoic acid(M. P. -183 C.) crystallize off. The yield amounts to 60%. Afterre-crystallization in boiling water the resulting product melts at 188C. If the amination reaction is carried out at 30 C., the reactionproduct predominantly comprises amino-didecanoic acid.

Similar procedures may be used for the amination of other(ii-halogenated acids such as wbromobutanoic acid, w-bromovalerianicacid, and w-bromostearic acid.

It will be understood that the details of procedure described, and theexemplary compositions given, are merely illustrative and in no wayrestrictive of the scope of the invention.

What I claim is:

1. A method for producing an w-amino carboxylic acid selected from thegroup consisting of Q-amino nonanoic acid and 10-amino decanoic acidwhich comprises reacting an aqueous ammonia solution with anw-halogenated acid selected from the group consisting ofw-monohalogenated nonanoic and decanoic acids for a period of from aboutsix to about twenty days, at a temperature between about 0 C. and about15 C.

2. A method for producing 9-amino nonanoic acid which comprises reactingan aqueous ammonia solution with w-halogenated nonanoic acid for aperiod of about twenty days at a temperature between about 0 C. andabout 5 C.

3. A method for producing 10-amino decanoic acid which comprisesreacting an aqueous ammonia solution with w-monohalogenated decanoicacid for a. period of from about six to about ten days at a temperaturebetween about 10 C. and about 15 0.

References Cited in the file of this patent UNITED STATES PATENTS

1. A METHOD FOR PRODUCING AN W-AMINO CARBOXYLIC ACID SELECTED FROM THEGROUP CONSISTING OF 9-AMONO NONANOIC ACID AND 10-AMINO DECANOIC ACIDWHICH COMPRISES REACTING AN AQUEOUS AMMONIA SOLUTION WITH ANW-HALOGENATED ACID SELECTED FROM THE GROUP CONSISTING OFW-MONOHALOGENATED NONANOIC AND DECANOIC ACIDS FOR A PERIOD OF FROM ABOUTSIX TO ABOUT TWENTY DAYS, AT A TEMPERATURE BETWEEN ABOUT 0* C. AND ABOUT15* C.